Capuzzo 2006

Methods	Randomized, double‐blind, placebo‐controlled study Location: Italy Study design: parallel, 2‐armed
Participants	A total of 150 patients randomized, 12 did not complete 138 patients completed: 67 in melatonin group and 71 in placebo group Age: melatonin 73.2 ± 5.9, placebo 72.1 ± 5.4 Gender (M/F) in %: melatonin (48/52), placebo (52/48) ASA class: I‐III Type of surgery: elective surgery Type of anaesthesia: general or spinal Baseline (anxiety, pain) described: yes, yes
Interventions	Melatonin: 10 mg Placebo Administration route: oral Time of administration: 90 min preoperatively
Outcomes	1. Anxiety measured by numerical rating scale (0 to 10) (pre‐ and postoperative) 2. Depression measured by numerical rating scale (0 to 10) 3. Pain measured by numerical rating scale (0 to 10) 4. Satisfaction with anaesthesia (0 to 100) 5. Cognitive function (Frontal Assessment Battery and Babcock Story Recall Test)
Notes	Sample size calculation: described Author (Capuzzo M) contacted by e‐mail 4 July 2013: investigators and assessors blinded. Mistake in the dropout numbers in the 2 groups; should be 4 in the placebo group and 8 in the melatonin group
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The pharmacist prepared, by computer‐generated randomization, 150 sealed envelopes, each reporting a code number and containing 2 capsules. Each indistinguishable capsule contained either 5 mg melatonin or placebo." (page 121) (Capuzzo 2006)
Allocation concealment (selection bias)	Low risk	Quote: "The pharmacist prepared, by computer‐generated randomization, 150 sealed envelopes, each reporting a code number and containing 2 capsules. Each indistinguishable capsule contained either 5 mg melatonin or placebo." (page 121)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Patients not completing the study were almost balanced in numbers across intervention groups and with similar reasons for lack of completion
Selective reporting (reporting bias)	Unclear risk	Study protocol not available
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Patients and personnel blinded. Quote: "indistinguishable capsules" (page 121)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors and investigator blinded (confirmed by e‐mail contact with the author)